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Sirolimus Combined With ATRA for the Treatment of Auto-Immune Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04324411
Recruitment Status : Not yet recruiting
First Posted : March 27, 2020
Last Update Posted : March 27, 2020
Information provided by (Responsible Party):
Bing Han, Peking Union Medical College Hospital

Brief Summary:
Autoimmune anemia (AIA), including autoimmune hemolytic anemia (AIHA), EVENs' syndrome (ES), acquired pure red aplastic anemia (PRCA), is a kind of anemia disease mediated by autoimmunity, which can be primary or secondary to other diseases including autoimmune disease, malignant tumor, infection, etc. Glucocorticoid is the first-line treatment. However, the recurrence rate is very high and some patients may not response to steroids, the latter defined as refractory autoimmune anemia (RAIA). Second-line therapies include cyclosporine A (CSA), cyclophosphamide, 6-mercaptopurine, CD20 monoclonal antibody, anti human lymphocyte immunoglobulin (ATG), and even splenectomy. Cyclosporine A is easy to accept while some patients may have side effects such as renal function damage, gingival hyperplasia, hypertension and so on. Other second-line drugs also have many problems, such as low effective rate, slow onset, expensive price, and large side effects, and some patients do not response to these treatments. The refractory/relapsed AIA patients have increased cardiovascular events, increased opportunities for infections, decreased quality of life, and even death. At present, there is still no effective treatment for these patients. Our previous retrospective study showed that sirolimus was effective in cyclosporine refractory PRCA with an effective rate of 70% and slight side effects. In addition, we used sirolimus in refractory AIHA and ES, with an effective rate of 60-70%. However, there are still some non-responsive patients. Recently, it has been reported that all trans retinoic acid (ATRA) combined with danazol was effective in the treatment of refractory immune thrombocytopenic purpura (ITP). Therefore, we plans to combine sirolimus and ATRA in the treatment of refractory AIA to improve the efficacy. Since both sirolimus and ATRA are cheap and have slight side effects, this combination may reduce the economic burden of patients and reduce the side effects related to treatment.

Condition or disease Intervention/treatment Phase
Autoimmune Anemia Drug: sirolimus and ATRA Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sirolimus Combined With All Trans Retinoic Acid for the Treatment of Auto-Immune Anemia
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
Drug Information available for: Sirolimus

Arm Intervention/treatment
Experimental: treatment group
combined sirolimus(serum concentration to be 4-10ng/ml) and ATRA (20mg bid) for at least 6 months
Drug: sirolimus and ATRA
sirolimus (serum concentration 4-10ng/ml) and ATRA 20mg bid

Primary Outcome Measures :
  1. overall response rate [ Time Frame: 1 year ]
    overall response rate

  2. rate of side effects [ Time Frame: 1 year ]
    rates and types of all side effects

Secondary Outcome Measures :
  1. change of HGB concentration [ Time Frame: through study completion, an average of 1 year ]
    change of HGB concentration

  2. frequency of HGB transfusion [ Time Frame: through study completion, an average of 1 year ]
    frequency of HGB transfusion

  3. time to response [ Time Frame: through study completion, an average of 1 year ]
    time to response

  4. response duration [ Time Frame: through study completion, an average of 1 year ]
    CR/PR duration

  5. life quality score (SF 36) [ Time Frame: through study completion, an average of 1 year ]
    life quality score

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. diagnosed as autoimmune anemia (autoimmune hemolytic anemia, pure red aplastic anemia, events syndrome) without organ complications;
  2. ineffective, relapsed or intolerant patients who have been treated with at least one kind of sufficient current conventional drug (steroids, CsA, CD20 monoclonal antibody, tacrolimus and others) ;
  3. normal cardiac function, liver function (total bilirubin ≤ 1.5 × ULN, ALT/AST ≤ 3.0 × ULN) and renal function (serum creatinine ≤ 1 × ULN);
  4. no secondary disease;
  5. unable to accept hematopoietic stem cell transplantation;
  6. ECoG score ≤ 2;
  7. able to sign the informed consent form.

Exclusion Criteria:

  1. failure to make a definite diagnosis;
  2. AIA secondary to known diseases such as systemic lupus erythematosus, rheumatoid arthritis, tumor or other inflammatory diseases;
  3. severe hepatorenal insufficiency (creatinine, transaminase more than 3 times of the upper limit of normal value);
  4. uncontrollable systemic infection or other serious diseases;
  5. pregnant or lactating women;
  6. patients with mental disease who are unable to sign the informed consent;
  7. taking other AIA drugs or stopping the drugs for less than 3 months;
  8. allergic to the study drug;
  9. participation in other clinical studies;
  10. patients in any other circumstances considered unsuitable by the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04324411

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Peking union medical college hospital
Beijing, China
Sponsors and Collaborators
Peking Union Medical College Hospital
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Responsible Party: Bing Han, Professor, Peking Union Medical College Hospital Identifier: NCT04324411    
Other Study ID Numbers: sirolimus-3
First Posted: March 27, 2020    Key Record Dates
Last Update Posted: March 27, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: individual participant data would be accepted upon request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: always
Access Criteria: email request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Hematologic Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs